What kind of separation techniques are used at industrial scale for chiral compounds? I wish to synthesize some compounds at laboratory scale and later implement it at commercial scale. But I am afraid that how a chiral mixture will be purified at such a large scale.
Any ideas/references/comments/suggestions are welcome.
Thanks
Sachin. A good question and something that must be investigated early on in the process as some compounds can not be economically processed or synthesized in their single enantiomeric form on a commercial scale. We initially try and skip using expensive chromatography methods for purification and either just attempt to synthesize the pure enantiomer first or try crystallization or simple extraction methods (liquid/liquid). These techniques can and should be tried at bench scale first. Results vary...
I have processed many types of pharmaceutical compounds (esp chiral) from analytical to full commercial scale-up over the past decades and each one is different. However, when starting out, the same basic questions must be asked and the same initial experiments run to find out what methods will be suitable to use for that specific sample. For scale up you need to consider many things. If you have poor resolution at analytical scale, then scale-up may be very challenging and expensive. Many methods and techniques should be tested at analytical scale to find suitable methods. You do not want to do this at prep scale! Work out as many of the details early in the process. One of the first factors which should be addressed is of course compound potency (if the compound demonstrates effectiveness at extremely low concentrations, then it may be less costly to produce). Other factors include the cost of solvents and materials used, their availability (in the purity needed), temperature at which the process will take place, stability of the material in solution and time needed. Popular large scale chromatographic separation techniques include: Preparative HPLC, Simulated Moving Bed / Countercurrent Chromatography and SFC.
Hello William Letter ,
Many thanks for your explanatory response. It helps.
What I can infer after reading your comment is that probably idea of separating the isomers of my planned monomers will not work at commercial scale. Therefore, I should try to tune my strategy in some other way which can make it less expensive and more effective.
Please correct me if I am wrong.
If you have racemic misture then your only real choice is resolution via crystalization, either normal or so called "Dutch resolution" or some kind of enzymatic resolution. This is very usefull if you can use both enantiomers of the product. If you have use only for one then its, in my opinion, start with enantioselective synthesis
Yes. The strategy to employ in such research is to always seek a method or technique which yields exactly what you want using the least number of complicated steps as possible. Keep it simple.
You may use kinetic resolution, chromatography resolution and membrane-based resolution.
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